We investigated the effect of caffeic acid phenethyl ester in rat ileum injury induced by chronic biliary obstruction. Swiss albino rats were divided into three groups: Group 1, sham (n = 7); Group 2, common bile duct ligation (n = 7); and Group 3, common bile duct ligation plus caffeic acid phenethyl ester (n = 7). In the caffeic acid phenethyl ester-treated rats, ileum tissue levels of malondialdehyde and myeloperoxidase were significantly lower than those of the bile duct-ligated rats (P < 0.001). The levels of tumor necrosis factor-alpha, interleukin-6, and interleukin-1 alpha in the caffeic acid phenethyl ester group were significantly lower than those in the bile duct ligation group (P < 0.03, P < 0.01, and P < 0.02 respectively). The present study demonstrates that intraperitoneal administration of caffeic acid phenethyl ester in bile duct-ligated rats reduces intestinal oxidative stress. This effect may be useful in the preservation of intestinal damage in cholestasis.